Preparation And Biological Application Of Fluorescent Probes Based On Salicylaldehyde-hydrazine Framework

Fluorescent techniques have become a powerful tool for exploring the microscopic world due to their high sensitivity,high specificity,rapid response,and easy operation.They have been successfully used in various fields such as fluorescence sensing,biological imaging,and clinical testing.Traditional organic fluorescent probes usually have an aggregation caused quenching(ACQ)effect,which greatly limits their application in aqueous and physiological environments.The concept of aggregation-induced emission(AIE)broke the shackles of ACQ and provided a new design strategy for fluorescent probe.The excited state intramolecular proton transfer(ESIPT)mechanism can make molecules have a great Stokes shift and effectively avoid self-absorption.Therefore,the development of fluorescent probes with the synergistic effect of AIE+ESIPT has great application value.keto-salicylaldehyde azine(KSA)is a novel AIE Building Block developed combining ESIPT process in our previous work.In this thesis,a series of fluorescent probes with "ESIPT+AIE" properties were developed based on KSA building block through structural modification and functionalization,and a systematic structure-activity relationship study of KSA building block has been carried out.And expanded the application of KSA molecules in specific subcellular organelles and microbial imaging and sterilization.The specific work is as follows:In chapter 1,we introduced the internal mechanism of the AIE and ESIPT process,summarized the recently reported applications of fluorescent probes with "ESIPT + AIE" properties in ion sensing and biological imaging.In addition,the KSA building block is introduced and the research results based on the KSA structure are briefly summarized.In chapter 2,we designed and developed a series of molecules with dual ESIPT luminescent cores using symmetrical bilateral salicylaldehyde derivatives as substrates,typical KSA structures DPAS and FAS,and typical ESIPT building groups HBT and HPBI as model compounds.The structure-activity relationship,responsiveness to metal ions and targeting of subcellular organelles of this series of molecules were studied.In chapter 3,we selected DPAS as a model compound,by systematically introducing substituents with different electronic effects and different steric effects at the K-terminal,a series of DPAS derivatives were designed and synthesized.The change trend of the probe behaviors caused by the change of the K-terminal structure was studied,the structure-activity relationship of the KSA building block was improved,and the abilities of KSA fluorescent probes to interact with microorganisms were preliminary explored.In chapter 4,we used the KSA building block as the luminescent core to introduce cationic groups through non-conjugated links,and synthesized a series of KSA-type cationic probes.Expanded the application of KSA based molecules to specific imaging of mitochondria,cell membranes and microorganisms.